title: Interaction of ataxin-3 with huntingtin-associated protein 1 through Josephin domain.
abstract: Huntingtin-associated protein 1 (HAP1) is an essential component of the stigmoid body (STB) and known as a possible neuroprotective interactor with causative proteins for Huntington's disease, spinal and bulbar muscular atrophy, spinocerebellar ataxia type 17 (SCA17), and Joubert syndrome. To clarify what other causative molecules HAP1/STB could interact with, we cloned normal causative genes for several neural disorders from human brain RNA library and evaluated their subcellular interaction with HAP1/STB by immunocytochemistry and immunoprecipitation after cotransfection into Neuro2a cells. The results clearly showed that HAP1/STB interacts with the normal ataxin-3 through Josephin domain and polyglutamine-expanded mutants derived from SCA3 as well. The findings suggest that HAP1/STB could modify the physiological function of normal ataxin-3 and pathogenesis of SCA3 attributable to the mutant ataxin-3.
authors.affiliation: Department of Neuroscience, Yamaguchi Graduate University School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Takeshita
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Fujinaga
authors.forename: Keiji
authors.initials: K
authors.lastname: Kokubu
authors.forename: Md Nabiul
authors.initials: MN
authors.lastname: Islam
authors.forename: Mir Rubayet
authors.initials: MR
authors.lastname: Jahan
authors.forename: Akie
authors.initials: A
authors.lastname: Yanai
authors.forename: Akira
authors.initials: A
authors.lastname: Kakizuka
authors.forename: Koh
authors.initials: K
authors.lastname: Shinoda
mesh_terms: D000067699:Ataxin-3; D015153:Blotting, Western; D006801:Humans; D047468:Immunoprecipitation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020754:Spinocerebellar Ataxias / Q000378:metabolism; D014162:Transfection
chemical_list: C096896:HAP1 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3